Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Korea.
Nucleic Acids Res. 2010 Oct;38(19):6389-403. doi: 10.1093/nar/gkq491. Epub 2010 Jun 8.
The dynamic exchange of histone lysine methylation status by histone methyltransferases and demethylases has been previously implicated as an important factor in chromatin structure and transcriptional regulation. Using immunoaffinity TAP analysis, we purified the WHISTLE-interacting protein complexes, which include the heat shock protein HSP90α and the jumonji C-domain harboring the histone demethylase JMJD1C. In this study, we demonstrate that JMJD1C specifically demethylates histone H3K9 mono- and di-methylation, and mediates transcriptional activation. We also provide evidence suggesting that both WHISTLE and JMJD1C performs functions in the development of mouse testes by regulating the expression of the steroidogenesis marker, p450c17, via SF-1-mediated transcription. Furthermore, we demonstrate that WHISTLE is recruited to the p450c17 promoter via SF-1 and represses the transcription of prepubertal stages of steroidogenesis, after which JMJD1C replaces WHISTLE and activates the expression of target genes via SF-1-mediated interactions. Our results demonstrate that the histone methylation balance mediated by HMTase WHISTLE and demethylase JMJD1C perform a transcriptional regulatory function in mouse testis development.
组蛋白赖氨酸甲基化状态的动态交换由组蛋白甲基转移酶和去甲基化酶介导，先前被认为是染色质结构和转录调控的重要因素。使用免疫亲和 TAP 分析，我们纯化了 WHISTLE 相互作用蛋白复合物，其中包括热休克蛋白 HSP90α 和含有组蛋白去甲基酶 JMJD1C 的 jumonji C 结构域。在这项研究中，我们证明 JMJD1C 特异性地去甲基化组蛋白 H3K9 单甲基化和二甲基化，并介导转录激活。我们还提供了证据表明，WHISTLE 和 JMJD1C 都通过调节类固醇生成标记物 p450c17 的表达，在通过 SF-1 介导的转录调控的小鼠睾丸发育中发挥功能。此外，我们证明 WHISTLE 通过 SF-1 被募集到 p450c17 启动子上，并抑制青春期前阶段的类固醇生成的转录，随后 JMJD1C 通过 SF-1 介导的相互作用取代 WHISTLE 并激活靶基因的表达。我们的研究结果表明，由 HMTase WHISTLE 和去甲基化酶 JMJD1C 介导的组蛋白甲基化平衡在小鼠睾丸发育中发挥转录调控功能。
